Vimentin is sufficient and required for wound repair and remodeling in alveolar epithelial cells

• Published in: The FASEB journal Vol. 25; no. 11; p. 3873
• Main Authors: Rogel, Micah R, Soni, Pritin N, Troken, James R, Sitikov, Albert, Trejo, Humberto E, Ridge, Karen M
• Format: Journal Article
• Language: English
• Published: United States 01.11.2011
• Subjects: Animals; Cell Line; Cell Movement - drug effects; Cell Proliferation - drug effects; Humans; Male; Pulmonary Alveoli - cytology; Rats; Smad Proteins - physiology; Transforming Growth Factor beta1 - physiology; Vimentin - biosynthesis; Vimentin - physiology; Wound Healing - physiology
• DOI: 10.1096/fj.10-170795

The physiological and pathophysiological implications of the expression of vimentin, a type III intermediate filament protein, in alveolar epithelial cells (AECs) are unknown. We provide data demonstrating that vimentin is regulated by TGFβ1, a major cytokine released in response to acute lung injury and that vimentin is required for wound repair and remodeling of the alveolar epithelium. Quantitative real-time PCR shows a 16-fold induction of vimentin mRNA in TGFβ1-treated transformed AECs. Luciferase assays identify a Smad-binding element in the 5' promoter of vimentin responsible for TGFβ1-induced transcription. Notably, TGFβ1 induces vimentin protein expression in AECs, which is associated with a 2.5-fold increase in cell motility, resulting in increased rates of migration and wound closure. These effects are independent of cell proliferation. TGFβ1-mediated vimentin protein expression, cell migration, and wound closure are prevented by a pharmacological inhibitor of the Smad pathway and by expression of Ad-shRNA against vimentin. Conversely, overexpression of mEmerald-vimentin is sufficient for increased cell-migration and wound-closure rates. These results demonstrate that vimentin is required and sufficient for increased wound repair in an in vitro model of lung injury.